Biomedical subjects

B C Hansen

Publications and source records attributed to B C Hansen.

At least 91 records · Page 5Linked to original sources

PubMed1989

Peripheral neuropathy in diabetic monkeys.

Peripheral neuropathy is a significant complication of human diabetes and a source of morbidity. Appropriate experimental models may aid in understanding its pathogenesis and in developing therapeutic strategies. We sought to determine whether spontaneously diabetic obese adult monkeys developed peripheral neuropathy and whether it occurred early or late in relation to the onset of hyperglycemia. We studied nerve conduction in both motor (peroneal, median, and ulnar) and sensory (median and ulnar) nerves in 13 adult male rhesus monkeys, 4 overtly diabetic and 9 nondiabetic (mean age 21 +/- 2 and 16 +/- 2 yr, respectively, NS; mean fasting plasma glucose 14.5 +/- 3.4 and 4.4 +/- 0.6 mM, P = .001). The diabetic animals had significantly reduced motor conduction velocities and prolonged F-wave latencies. Motor-evoked amplitudes did not differ. In the diabetic monkeys, nerve conduction times were increased in motor fibers, which could be identified as early as 2 yr after the onset of hyperglycemia. These abnormalities are similar to those seen in humans and suggest further study of these animals as a primate model of human diabetic neuropathy.

Animals↗

PubMed1988

Metabolic clearance rates of synthetic human growth hormone in lean and obese male rhesus monkeys.

The MCR of synthetic human GH was studied in eight adult male rhesus monkeys (Macaca mulatta). Four monkeys were lean (less than 20% body fat), and four were obese (greater than 35% body fat). The monkeys were given a single bolus injection of GH (2.5 micrograms/kg BW), followed by a constant infusion of GH (250 micrograms/h) for 2.5 h. Venous blood samples were collected before the infusion and every 10 min during the infusion. In both groups a plateau of the plasma GH concentrations, indicating a steady state, was reached 70 min after the start of the infusion. The MCR of GH was calculated from the ratio of the constant GH infusion rate and the plateau plasma GH concentration in each monkey. The MCR of synthetic GH was 12.7 +/- 1.7 (+/- SD) L/24 h in the lean group and 19.5 +/- 2.9 L/24 h in the obese group (P less than 0.007). However, the MCR/kg ratio in the lean monkeys was the same as that in the obese animals. We conclude that 1) MCR of GH is directly proportional to body weight; and 2) the lower plasma GH levels in obesity may be due to an increase in its MCR not compensated for by an appropriate increase in the rate of GH secretion.

Age Factors↗

PubMed1988

Dietary considerations for obese diabetic subjects.

Individuals with an upper-body form of obesity show greater associations with higher glucose excursions, exacerbated insulin resistance, increased abnormality of lipoprotein profile, and higher cardiovascular risk. Individuals with obesity and diabetes are at great risk for cardiovascular disease. Weight reduction and improvement in blood glucose control through dietary interventions for the obese person with non-insulin-dependent diabetes mellitus (NIDDM) hold the greatest potential for reducing morbidity and mortality. The relative merits of different weight-reduction programs are unclear, but regimens should be nutritionally complete, easy to follow, and include a program for maintaining the reduced weight level. Improvement in insulin action and the possibility of slowing development of clinical nephropathy or end-stage renal disease in NIDDM through weight loss have been found. Very low calorie diets, when used with medical supervision, may lead to significant weight loss, improved metabolic status, and even reduction or elimination of the need for oral hypoglycemic agents or insulin; however, further studies are needed to examine possible negative outcomes in people with NIDDM before very low calorie diets can be recommended. The causes of obesity and its connection with diabetes are unclear, but even modest calorie restriction may be beneficial to obese diabetic patients because of the positive effects on blood glucose levels and requirements for insulin and oral antidiabetic agents.

Body Weight↗

PubMed1988

Changes in insulin responses and binding in adipocytes from monkeys with obesity progressing to diabetes.

To gain insight into cellular events associated with the progression of obesity to diabetes, we have studied glucose metabolism and insulin responses in adipocytes from monkeys with spontaneous obesity. Over a 3- period, we studied animals which (A) remained relatively lean; (B) became obese (over 30 percent body fat) with normal glucose tolerance; (C) were obese and developed hyperinsulinemia (over 100 microU/ml); and (D) were obese and subsequently developed noninsulin-dependent diabetes (NIDDM) (fasting plasma glucose above 140 mg/dl and abnormal glucose tolerance test). Adipocyte glucose utilization, evaluated by conversion of 14-C-glucose to CO2 and lipids, was measured in the absence and presence of varying concentrations of insulin, using cells prepared from biopsy samples of subcutaneous abdominal fat. The major change in adipocyte metabolism was a decrease in basal and insulin-stimulated glucose utilization in NIDDM, relative to the enhanced responses observed in cells from the obese-hyperinsulinemic monkeys. Longitudinal studies of individual monkeys over 2-3 years led to the following additional observations regarding adipocyte glucose metabolism. Basal and insulin-stimulated glucose utilization dropped markedly as hyperinsulinemia progressed into diabetes. As impairments in glucose tolerance worsened in diabetes, adipocytes showed only a modest or negligible additional impairment in basal and insulin-stimulated glucose oxidation. Insulin binding was reduced in adipocytes from monkeys with obesity as compared to lean controls, and was similar in cells from monkeys with obesity and NIDDM. In the monkeys, obesity was initially associated with enhanced adipocyte metabolism. With the spontaneous development of NIDDM, glucose metabolism in adipocytes was depressed. The progression of metabolic events from hyperinsulinemia to NIDDM in monkeys includes cellular changes in insulin responses at the level of the adipocyte.

Adipose Tissue↗

PubMed1987

Effects of different heat treatments during processing of soybean meal on nursery and growing pig performance.

Four soybean meals (SBM) were manufactured in a commercial solvent-extraction plant to give a much wider range in heat treatment than is usually found among commercially available SBM. The SBM were designated in ascending order of heat treatment as Under, Normal, Over and Rumen Escape. The nutritive value of the four meals was evaluated in a series of five feeding trials using 458 pigs: two performance and two diet preference trials with pigs weaned at 4 wk of age and one performance trial with growing pigs (17.4 kg initial weight were conducted). In both nursery and grower trials, there were no differences (P greater than .10) in performance of pigs fed the four meals. However, in the nursery trials, the severely heated meal (Rumen Escape) supported slightly lower gains (6.4%) and less desirable feed efficiency (3.5%) than the average of the other three meals. Growing pig performance was essentially the same for all meals. This suggests that older pigs either used the Rumen Escape meal more effectively than nursery pigs, or the Rumen Escape diet contained adequate digestible lysine for 17.4-kg pigs to grow optimally. In the preference studies, pigs selected between Normal- and Rumen Escape-supplemented diets. Pigs consumed 63 and 62% of the Normal diet in preference trials 1 and 2, but these differences were not significant (P greater than .10) due to the large variation among pens. These data suggest that the range of heat treatment normally found among commercially available SBM (Under, Normal and Over meals) has no effect on the nutritive value of the meal for swine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗

PubMed1986

Heterogeneity of insulin responses: phases leading to type 2 (non-insulin-dependent) diabetes mellitus in the rhesus monkey.

To determine the natural history of the development of Type 2 (non-insulin-dependent) diabetes mellitus, basal plasma insulin and glucose levels and responses to intravenous glucose tolerance tests were determined over a period of 6 years in 42 adult male rhesus monkeys (Macaca mulatta). Among the 28 obese monkeys (percent body fat greater than 22%) over the age of 10 years, 9 developed overt Type 2 diabetes (fasting plasma glucose, greater than 7.8 mmol/l, and reduced glucose disappearance rates, KG less than 1.5), and 14 monkeys have shown progressive changes which suggest that they may also become diabetic. Application of a highly constant antecedent diet and a consistent 16-h fast minimized experimental variability, and permitted the identification of 8 phases in the progression from normal lean young adult to overt Type 2 diabetes. The earliest changes which could be detected were a slight increase followed by a progressive rise in fasting plasma insulin levels and an increased insulin secretion in response to a glucose stimulus. These events preceded by several years the onset of a gradual deterioration of glucose tolerance. We found that hyper-, normo-, or hypoinsulinaemia could be associated with normoglycaemia or varying degrees of hyperglycaemia; however, the prospective longitudinal study of individual monkeys clearly identified this apparent heterogeneity of plasma insulin and glucose levels as reflecting sequential changes in a continuum of events preceding or accompanying the development of impaired glucose tolerance and Type 2 diabetes mellitus.

Animals↗

PubMed1985

Nutrient composition: effects on appetite in monkeys with oral factors held constant.

The effects of macronutrients on appetite and total caloric intake in monkeys (Macaca mulatta) was studied using a new feeding and infusion system which yoked intragastric infusion of various nutrients to oral ad lib intake and removed the confounding factor of palatability from the assessment of nutrient effects on feeding behavior. A suction-activated liquid diet feeding system provided free access to a nutritionally complete diet, with 1 ml of diet delivered orally by pump with each discrete suck by the monkey. A second pump was yoked to the oral feeding pump and delivered various nutrients directly into the stomach via an implanted intragastric cannula. Thus, while oral diet composition remained constant, the net diet reaching the stomach varied over ranges of 28 to 77% carbohydrate, 16 to 65% fat and 7 to 36% protein. No significant differences in total caloric intake were observed between intakes of diets with net composition of high carbohydrate or high fat. When protein was increased to 36%, total caloric intake was generally reduced, and this effect was sustained for at least 3 weeks. Therefore, protein appears to have an increased specific satiating effect beyond the caloric content, when compared to carbohydrate or fat.

Animals↗

PubMed1985

Fluctuations in basal plasma levels of pancreatic polypeptide in monkeys and humans.

We reported that significant rapid oscillations occur in basal plasma levels of insulin, glucagon, and glucose in rhesus monkeys and humans. We searched for evidence for similar spontaneous fluctuations also in plasma levels of pancreatic polypeptide (PP). Mean +/- SE basal plasma levels of PP were 236 +/- 15 pg/ml in 11 monkeys, 64 +/- 12 in nine normal-weight human subjects, and 74 +/- 10 in nine obese human subjects. 1) PP levels fluctuated with periods of 6-26 min. The fluctuations in PP were less regular than and did not temporally correlate with the fluctuations in plasma levels of insulin, glucagon, or glucose (usual periods 8-12 min). 2) In human subjects the concentration but not the periodicity of PP was related to obesity. 3) Comparisons of simultaneously determined levels of PP in portal and central venous plasma of monkeys suggested that PP may be extracted to varying degrees by the liver, even under basal well-controlled conditions, and that neither the size of the PP portal-central gradient nor the period and amplitude of fluctuations was associated with PP concentration. We conclude that plasma PP levels fluctuate with such a large amplitude that these fluctuations must be considered in the interpretation of experimental results based on limited numbers of samples.

Adult↗

PubMed1985

Adiposity, anthropometric measures, and plasma insulin levels of rhesus monkeys.

In order to characterize spontaneous adult-onset obesity in a non-human primate model, we have studied a group of twenty-four obese and non-obese male rhesus monkeys (Macaca mulatta). The monkeys, ranging in age from 12 to 27 years, were defined as obese on the basis of tritiated water estimates of body fat content exceeding 25 percent of body weight. Although the obese and non-obese monkeys had similar crown-rump lengths, they differed significantly not only in body weight (17.0 +/- 3.2 vs 11.7 +/- 1.8 kg, X +/- s.d., P less than 0.001), and average body fat content (37.8 +/- 6.6 vs 13.2 +/- 5.4 percent, P less than 0.001) but also in midgirth circumferences (57.5 +/- 8.4 vs 34.8 +/- 6.2 cm, P less than 0.001) and abdominal (but not triceps or scapular) skinfold thicknesses (22.74 +/- 5.8 vs 9.82 +/- 1.82 mm, P less than 0.001), thus, indicating the predominantly abdominal distribution of the fat mass. A new Obesity Index Rh, for rhesus monkeys, defined as body weight divided by the square of the crown-rump length, was developed as an adaptation of obesity indices used for humans and rats. The high correlation of the Obesity Index Rh with percent body fat and its relative independence of height make possible future identification of obese rhesus monkeys on the basis of anthropometric measurements. There were slight, but not significant, differences between the obese and the non-obese groups in lean body mass (10.9 +/- 2.8 vs 8.8 +/- 1.8 kg) and in fasting plasma glucose levels (87.1 +/- 31.8 vs 63.2 +/- 7.5 mg/dl). Obese monkeys had significantly larger average fat cell sizes (1.29 +/- 0.54 vs 0.61 +/- 0.29 microgram lipid/cell, P less than 0.05) and significantly greater fat cell numbers (6.1 X 10(9) vs 2.2 X 10(9), P less than 0.01). Fat cell numbers were better correlated with body weight and total body fat parameters than fat cell size, while fat cell size was more closely associated with the log of fasting plasma insulin levels than was fat cell number. The similarities to studies in humans indicate the importance of the spontaneously obese adult rhesus monkey as an animal model in the study of obesity.

Adipose Tissue↗

PubMed1984

Feeding behavior during experimentally induced obesity in monkeys.

In order to investigate the effects of the induction and remission of obesity on feeding behavior, male rhesus monkeys were made obese by sustained intragastric (IG) feeding of a complete liquid diet. Intragastric diet infusion levels of 100, 125, 145, and 165% of the baseline oral intake of each monkey were successively administered. During the initial overfeeding period (100% of the baseline oral intake), at least one week was required to reduce voluntary oral intake to less than 25% of the baseline levels and complete suppression of oral intake did not occur. This increased total caloric intake (IG infusion plus oral intake) resulted in a rapid rate of weight gain of at least 5 times the baseline rate. With successive increases in caloric infusion level, oral intake was eventually suppressed, and rapid weight gain was sustained. When the IG infusion was abruptly terminated after 50 to 130 days, 3 monkeys refused all food for 14 to 35 days. The monkeys' oral intakes stabilized three to ten weeks after the end of the overfeeding period. The length of this period prior to the resumption of normal oral intake was not related to length of overfeeding nor to the amount of weight gained. The monkeys' body weights dropped rapidly in the initial post-overfeeding period and then stabilized, sometimes at levels higher than their baseline body weights. In 2 monkeys, at the end of overfeeding the amounts infused were gradually reduced in order to determine the calories required to maintain their body weights at peak levels. Significantly fewer kcal/kg were required to maintain peak body weights than were ingested during the baseline periods.

Animals↗

PubMed1984

Hormonal changes: are they useful in the classification of obesities?

Changes in hormonal levels and/or actions have frequently been implicated as either antecedent or concomitant factors in the etiology and progression of obesity. Therefore, various hormones are likely to be important in a classification schema for the obesities. Using selected hormones and experimental approaches as examples, this review emphasizes the complexity associated with the multiple measurable aspects of hormone levels and functions, and identifies some of the problems associated with simplistic or uni-dimensional assessments of hormonal factors in obesity. A framework is presented for the evaluation of each hormone for its possible contribution to a classification of the obesities.

Animals↗

PubMed1983

Cholecystokinin effects on feeding, glucose, and pancreatic hormones in rhesus monkeys.

The effects of cholecystokinin on feeding, and on plasma glucose and pancreatic hormone responses to a mixed-meal were determined in lean rhesus monkeys. Following an overnight fast the octapeptide of cholecystokinin (CCK-8) was administered intravenously over a 6 minute period coincident with the initiation of free feeding or an intragastric infusion of a mixed liquid diet. CCK-8 inhibited feeding and delayed the plasma glucose and insulin response to a mixed-meal. The threshold for the feeding effect ranged from 30 to 120 ng/kg/min across monkeys and did not extend beyond 15 minutes of the start of the CCK infusion. The delays in plasma glucose and insulin were not dependent on rate or amount of food entering the stomach. Further, there were no alterations from basal levels in plasma glucose or insulin prior to the onset of CCK-induced feeding inhibition. There was no evidence that CCK-8 stimulated insulin release, nor was the usual close relationship between plasma glucose and insulin levels in response to a mixed-meal changed by CCK-8.

Animals↗

PubMed1982

Rapid fluctuations in plasma catecholamines in monkeys under undisturbed conditions.

We have demonstrated in monkeys and in man sustained synchronous oscillations in plasma levels of insulin, C-peptide, glucagon, and glucose that have periods ranging from 8 to 11 min. To identify the mechanisms of these oscillations, we studied plasma levels of catecholamines in search for periodic fluctuations. Blood was obtained at 2-min intervals from fasting, undisturbed, chair-adapted male rhesus monkeys via chronically implanted central venous catheters. Plasma levels of epinephrine, norepinephrine, and dopamine were measured by a radioenzymatic assay. Large fluctuations in plasma epinephrine were observed with an average peak-to-trough amplitude of 34 pg/ml at a mean level of 122 pg/ml. Similar fluctuations in norepinephrine and dopamine occurred and were correlated to those of epinephrine: r = 0.51 and 0.35, respectively. The most common periodicity in all three catecholamines was 6-13 min/cycle as determined by spectral analyses. Cross-correlation analyses indicated that fluctuations in the catecholamines were significantly negatively correlated with oscillations in insulin and were unrelated to fluctuations in glucagon. These fluctuations in plasma catecholamines may be related to mechanisms controlling the periodicity observed in plasma insulin and glucose.

Animals↗

PubMed1982

Influence of nutritional state on periodicity in plasma insulin levels in monkeys.

Rapid sustained oscillations in basal plasma levels of insulin, glucose, and glucagon (9-12 min/cycle) have been identified in rhesus monkeys and in humans. To assess the possible regulatory role of nutritional state in the control of these plasma fluctuations, 12 chronically cannulated conscious rhesus monkeys were studied at varying intervals following ingestion of a mixed meal. Blood samples were withdrawn at 2-min intervals for periods of 10-30 min. In the postprandial period both absolute and relative amplitudes (half amplitude percent) of oscillations increased up to 16 h postfeeding to maximal amplitudes of +/- 32% for insulin, +/- 4% for glucose, and +/- 22% for glucagon. Periods were consistently in the 9- to 12-min range for insulin and glucose. Progressive deprivation to 88 h produced decreases in amplitudes and more irregularity in fluctuations but did not affect the underlying periodicity of these oscillations in plasma levels of insulin, glucose, and glucagon. Results are consistent with the existence of one or more inherent oscillators in the pancreas that act to synchronize the release of hormones from particular types of islet cells. The amplitude of these oscillations but not the frequencies is associated with changes in liver metabolism and nutritional state.

Animals↗

PubMed1982

Fluctuations in basal levels and effects of altered nutrition on plasma somatostatin.

Rapid oscillations in basal plasma levels of insulin, C-peptide, glucagon, and glucose in rhesus monkeys have been reported previously. We now report large minute-to-minute fluctuations in plasma somatostatinlike immunoreactivity (SLI) in undisturbed, chair-adapted, and chronically cannulated male rhesus monkeys. Plasma samples were drawn from eight monkeys at 1- to 2-min intervals for 30-40 min following an overnight fast. Large fluctuations in SLI levels with periods of 4.4-9.4 min/cycle and possibly secondary periods of 14-18 min/cycle with average amplitudes of +/- 23% relative to the respective mean SLI levels were observed both within a single experiment and across monkeys under basal conditions. No consistent relationship was found between SLI fluctuations and that of insulin or glucagon. When portal and central blood samples were drawn precisely simultaneously no consistent portal-central gradient was found. Patterns of fluctuations in central and portal SLI levels were not correlated. Overfeeding significantly increased insulin levels but did not alter SLI levels. After 5 days of food deprivation basal SLI levels were unchanged. These data indicate the need to exercise care in the interpretation of single samples in the measurement of plasma SLI levels. Somatostatin secreted into the blood under basal, unstimulated conditions appears to be unrelated to nutritional balance.

Animals↗

PubMed1982

Rapid oscillations in plasma insulin, glucagon, and glucose in obese and normal weight humans.

We have previously identified in fasting monkeys large amplitude, rapid oscillations in plasma levels of insulin, glucagon, and glucose. To determine whether such spontaneous oscillations also occur in man, we studied 9 healthy normal weight subjects and 11 obese volunteers (145-316% ideal body weight). During the morning hours after a 16-h fast, peripheral venous blood was withdrawn at precise 1- or 2-min intervals over 40-120 min. Spectral analysis of the assay results showed significant oscillations in plasma levels of insulin and glucose, with periods ranging from 8-16 min (P less than 0.05). In this range, the means of the oscillatory periods in normal weight subjects were 12.1 +/- 1.0 min for insulin and 11.2 +/- 0.8 min for glucose. The oscillatory periods on obese subjects were not different from those in normal weight subjects (12.4 +/- 0.7 min for insulin and 12.1 +/- 0.9 min for glucose). Periodicity in plasma levels of glucagon was observed in the range of 12-23 min. Based on cross-correlation analysis, the periodic fluctuations in insulin, glucose, and glucagon showed no consistent relationships; the patterns observed did not support the presence of feedback loops among these parameters as the mechanism of these spontaneous fluctuations. Our data indicate that basal plasma levels of insulin, glucagon, and glucose fluctuate rapidly in man. The physiological function of these oscillations is yet to be identified; they may play a role in the regulation of responsiveness of the respective target tissues or of their own release into the circulation.

Adult↗

PubMed1981

Distress reduction and the effects of preparatory teaching films and patient control.

Fifty patients undergoing nasogastric intubation for gastric analysis participated in an experiment comparing the distress-reducing effects of four different types of information about an unpleasant procedure. Filmstrips depicted the procedure only; the procedure with common distressful sensations; the procedure with coping behaviors; and the procedure with coping behaviors to relieve common distressful sensations. Patients were also tested on their preference for control. Distress was measured by self-ratings on a 10-item Nasogastric Intubation Checklist. Pain, discomfort, and anxiety pre-, during, and postmanipulation- intubation were measured on a visual scale. Willingness to repeat the procedure was measured on a four-point scale. The study showed that: (a) Procedure with sensory and coping behavior information was effective in decreasing discomfort, pain, and anxiety for control and no-control preference subjects during and after the procedure, but was most effective in reducing intubation distress for subjects preferring no control. (b) Sensory information led to greater willingness to repeat the procedure. (c) Perceived control had little effect on distress reduction.

Adolescent↗

PubMed1981

Influence of somatostatin on gastric motility and meal absorption in rhesus monkeys, Macaca mulatta.

The effects of somatostatin on gastric motility and nutrient absorption from a mixed meal were evaluated in conscious rhesus monkeys (M. mulatta). Continuous saline or somatostatin (0.8 microgram/kg X min) infusions were carried out prior to and for 2 hr following an intragastric infusion of a complete liquid diet trace-labeled with 3H-3-glucose and 3H-9, 10-triolein. Gastric motility was assessed from recordings of gastric pressure and from extraluminal strain gauges. Intravenous somatostatin did not alter gastric motility or the rate of absorption of the labeled glucose; lipid absorption, however, was markedly impaired.

Animals↗